Cytogenetic Changes in Multiple Myeloma Timeline: A Tertiary Center's Experience

Introduction

Risk stratification in Multiple Myeloma according to cytogenetic abnormalities has been utilized clinically to guide understanding of prognosis. Specific cytogenetics abnormalities such as deletion 17p, t(14,16) and t(4,14) have been associated with more aggressive disease and poor outcome[1]. It has been postulated that genetic aberrations evolve in a temporal pattern in non-hyperploid multiple myeloma such that 13q deletion and t14q32 tend to be early events while chromosome 1 and 17 abnormalities occur as later events [2]. Furthermore, other studies have suggested higher frequencies of high risk cytogenetic abnormalities (such as deletion 17p and gain of 1q) at relapse after upfront autologous stem cell transplant [3]. Our study examined the cytogenetic profile of patients treated at a tertiary health system at the time of diagnosis and at first relapse, irrespective of bone marrow transplant and treatment

Methods

This is a retrospective study of patients treated at Henry Ford Cancer Institute/Henry Ford Health System. Subjects were adults diagnosed with multiple myeloma with relapse confirmed by a bone marrow biopsy between January 2014 and January 2019. The cytogenetic profile at time of diagnosis and relapse for each patient was reviewed. Exclusion criteria included history or current diagnosis of another malignancy. 145 cases were identified, of which 112 cases were excluded: 19 cases with plasmacytoma but no bone marrow relapse, 32 with other malignancy, 21 with relapse before study period, 5 with relapse after study period, and 35 with bone marrow biopsy or cytogenetics not available for review. As such, we analyzed the remaining 33 cases

Results

26 of the 33 cases underwent a bone marrow transplant. A third of the patients (11) developed new mutations, which included 17p deletion (3), 13q deletion (1), chromosome 1 abnormality (1), new trisomies (5), t(11,14) (4), hypoploidy (1), and IgH/CCDN1 changes (1).

Conclusion

Though cytogenetic evolution in multiple myeloma has been studied, not all patients undergo a bone marrow biopsy and cytogenetic evaluation at relapse, which limits this assessment. Despite our sample size being limited as a majority of the study population did not have cytogenetics recorded at relapse, our study reveals that new mutations can arise in a significant proportion of patients at relapse, some of which are known to be associated with poor prognosis. This can be potentially prognostic, as presence of new high-risk mutations could alter the presumed disease trajectory, and these could also have therapeutic consequences. While further studies with a larger sample size are needed to determine the frequencies of each mutation, our study underscores the importance of dedicated monitoring of cytogenetics at each relapse in multiple myeloma.

References

1. Palumbo, A., et al., Revised International Staging System for Multiple Myeloma: A Report From International Myeloma Working Group. J Clin Oncol, 2015. 33(26): p. 2863-9.

2. Jimenez-Zepeda, V.H., E. Braggio, and R. Fonseca, Dissecting karyotypic patterns in non-hyperdiploid multiple myeloma: an overview on the karyotypic evolution. Clin Lymphoma Myeloma Leuk, 2013. 13(5): p. 552-8.

3. Merz, M., et al., Longitudinal fluorescence. Haematologica, 2017. 102(8): p. 1432-1438.